In recent years, emphasis in acute renal failure (ARF) has been put not only on a structural abnormality, i.e., acute tubular necrosis, but also on a functional abnormality in renal hemodynamics. In diagnosis and therapy as well, a concept of ARF has been gradually replaced by that of acute kidney injury (AKI), and importance of early diagnosis and therapy has been advocated.
The acute kidney injury refers to a state in which renal function has rapidly deteriorated and the acute kidney injury is characterized by deterioration of renal function by tubular necrosis in many cases. Causes of the acute kidney injury include prerenal renal failure, intrinsic renal failure, and postrenal renal failure. The prerenal renal failure is caused when the kidneys are subjected to ischemia owing to a decrease in extracellular fluid volume through traumatic bleeding, dehydration, emesis, diarrhea, or the like, a reduction in effective circulating blood volume through cardiogenic shock or the like, and a decrease in renal blood flow through dissecting aortic aneurysm, renal artery thrombosis, or the like. The intrinsic renal failure involves direct injury caused in a renal tissue, such as glomerular injury (acute glomerulonephritis, rapidly progressive glomerulonephritis, polyarteritis nodosa, or the like), acute tubular necrosis (due to an antibiotic such as an aminoglycoside-based antibiotic, an anti-inflammatory analgesic, an antitumor drug, a contrast agent, or the like), or acute interstitial nephritis (due to an antibiotic such as a β-lactam-based antibiotic, an anti-inflammatory analgesic, an anticonvulsive drug, or the like). The postrenal renal failure involves urinary excretion disorder caused by occurrence of obstruction in the middle of a passage of urine, such as ureteral obstruction (ureteral calculi), bladder obstruction or urethral obstruction (prostatic hyperplasia, prostate cancer), or pelvic tumor.
The acute kidney injury includes many diseases that require ICU management because the diseases occur, for example, after open-heart surgery and aorta replacement. Hence the condition of the acute kidney injury needs to be grasped on an hourly basis after its development. Currently, no improvement in life prognosis of the acute kidney injury can be expected without early diagnosis and early therapeutic intervention.
Conventionally, diagnosis for the acute kidney injury has been performed based on serum creatinine and a urinary amount in ordinary cases. However, the diagnosis based on those two items has had a problem. No established diagnostic standards have existed for those two items, and 35 types of definitions of the acute kidney injury have existed. As a global approach to solving this problem, the Acute Kidney Injury Network has been established and proposed a diagnostic standard for the acute kidney injury. The diagnostic standard specifies that a diagnosis of acute kidney injury is made when the following conditions are satisfied: (1) serum creatinine increases by 1.5 times or more or by 0.3 mg/dL or more; and (2) oliguria at 0.5 mL/kg per hour continues 6 hours or more. Further, like a stage classification of chronic kidney disease, stage classifications of the acute kidney injury (RIFLE classification, AKIN classification, and the like) have been particularly proposed.
However, the diagnosis based on the two items still has a problem. Serum creatinine does not immediately increase even when a glomerular filtration rate decreases in association with kidney injury. However, serum creatinine may continue to increase for some time even when the glomerular filtration rate shows a tendency toward recovery. Accordingly, it cannot be said that serum creatinine is highly useful as each of an early marker for detecting an acute change and a marker for monitoring a therapeutic effect and predicting prognosis. In addition, serum creatinine is easily influenced by non-renal factors such as body weight, race, sex, drugs, muscle metabolism, and trophic condition. Further, the diagnosis based on a urinary amount requires a long period of time and hence the urinary amount is not suitable as a marker for the acute kidney injury, the condition of which needs to be grasped on an hourly basis after its development. Therefore, there is urgent need for development of a biomarker which allows easy measurement, is hardly influenced by other biological factors, and enables early detection, risk classification, and prognostic prediction of the disease.
As a substance found in association with a renal disease, there is known urinary podocalyxin, and there is disclosed a simple test measure for kidney injury involving measuring urinary podocalyxin (Patent Literature 1). Podocalyxin is a glycoprotein which is present in surfaces of podocytes constructing the renal glomerulus and is responsible for a filtration function. The podocytes are located on the Bowman's space side in the glomerular basement membrane and play important roles in the mechanism of glomerular filtration. Thus, it is known that the grasping of the degree of injury in the podocytes has an extremely important meaning in understanding a renal disease (Non Patent Literature 1). It is known that, in usual cases, urinary podocytes do not appear in non-glomerular renal disease and non-inflammatory glomerular renal disease, but do appear in inflammatory glomerular renal disease. Particularly in a case with robust findings in acute glomerular inflammation, a large number of podocytes appear (Non Patent Literatures 2 and 3). However, there is still no report on what behaviors the podocytes and podocalyxin show in the acute kidney injury resulting from various causes.